The FDA’s Office of Good Clinical Practice (OGCP) responds to inquiries on a variety of trial-related subjects, providing answers on the agency’s official regulations as well as best practices. The following is a selection of questions and answers excerpted from the CenterWatch publication, GCP Questions, FDA Answers.

Question: An investigator/site is refusing to allow our CRO’s monitor to physically view (in person) clinical trial materials, particularly central lab kit supplies and storage conditions. We have asked to do so on a mutually agreed regular basis, such as quarterly. The investigator/site believe that the sponsor/CRO should be able to provide the monitor with an inventory report of supplies shipped to the site (with expiration dates), as well as an accountability report of supplies used to then determine actual inventory at the site.

Per our SOPs, all monitors are required to:

• Inspect the storage conditions of laboratory kits, expiration dates and adequacy of supplies;
• Confirm that the site has adequate project/lab supplies and equipment per protocol requirements; and
• Verify the adequacy of other clinical project supplies (e.g., CRFs).

Also, this is documented in the site visit report under the question, “Does the site have adequate study supplies and required equipment as per protocol requirements (e.g. laboratory supplies)?”

The requirement to physically view (in person) seems to align with ICH E6 section 5.18.4 — Monitor’s Responsibilities:

“(b) Verifying that the investigator has adequate qualifications and resources (see 4.1, 4.2, 5.6) and remain adequate throughout the trial period, that facilities, including laboratories, equipment and staff, are adequate to safely and properly conduct the trial and remain adequate throughout the trial period.”

This is not something a monitor may verify verbally with site staff.

Answer: While monitoring is required by FDA regulations governing both pharmaceutical and device clinical studies, there are few specifics in the regulations and the only guidance in this regard that is presently available is very general. When FDA inspects either a sponsor or a clinical site, monitoring reports are commonly reviewed but any issues regarding noncompliance with regard to monitoring would be based on the FDA investigator’s direct observations. Lack of adequate monitoring can manifest itself in many ways. The main area in this regard that is tracked by FDA is sponsor compliance with the need to actually do study monitoring and the adequacy of any monitoring done. Inadequate monitoring (which would include complete lack of monitoring) is the most frequently cited noncompliance during sponsor inspections and this is true across all product types studied under FDA regulations.

It appears as the monitor you have a right to view the trial material as per your SOP. I am unclear if you are the sponsor. If you are not, you should contact the sponsor. Please see FDA’s monitoring guidance, Oversight of Clinical Investigations — A Risk-Based Approach to Monitoring at https://bit.ly/2VsXYPJ.

If the site still will not let your monitor review the study documents, you can make a complaint to FDA’s compliance office.

Question: We recently noted some investigational sites concerned with allowing monitors access to the pharmacy to perform drug accountability checks based on the site’s interpretation of the U.S. Pharmacopeia 800 guideline, Hazardous Drugs — Handling in Healthcare Settings.

As a CRO, we would like to clarify the role of the monitors in conjunction with this guidance in terms of what they may review in relation to hazardous drug preparation as well as any acceptable methods of review if it is deemed dangerous for a monitor to be present.

I am seeking to understand FDA’s view on this guidance in terms of monitor accountability/responsibilities at sites should they receive pushback from sites related to the aforementioned guidance.

Answer: OGCP cannot comment specifically on your question because we follow FDA regulations. However, we don’t see anything that would allow a site to forbid a monitor from entering an area to assess drug accountability. The monitors may have to wear personal protective equipment, but they would not be involved in the actual compounding, so that really shouldn’t be a big issue.

There doesn’t appear to be anything that prevents a monitor from doing what they need to do. If this continues, the sponsor can refuse to use sites that won’t allow for drug accountability monitoring. Sponsors would then not be able to ensure that the trial is conducted in accordance with the general investigational plan and protocols in the IND as required under 21 CFR 312.50.